Basophils and mast cells are highly specialized cells which synthesize and store a number of pharmacologically active mediators. These mediators can be released by antigen-antibody (IgE) interaction, by products of complement activation (C3a, C5a), and by a histamine releasing activity (HRA) present in supernatants from stimulated mononuclear cells. While much has been learned concerning the antigen-dependent release of mediators, less is known about the reactions triggered by activated complement fragments and HRA. We propose to compare and contrast the release of mediators (histamine, slow reacting substance, eosinophil chemotactic factor, and arginine esterase) in-vitro from both basophils amd mast cells by antigen, C5a and HRA. Basophils for these studies will be obtained from human and guinea pig blood. Human lung biopsies, human and baboon bronchial washings will be used for mast cell studies. Certain aspects of the mechanisms regulating release of mediators and the morphologic changes in stimulated cells will be explored. Basophils from patients with potential defects in the function of these cells will be studied. The discovery of HRA in this laboratory has recently been reported. We will characterize the production and the physico-chemical properties of this factor. Purified populations of T-cells, B-cells and macrophages will be used to clarify the cellular source of HRA. HRA will be compared with lymphocyte-derived mediators (lymphokines) important in cell-mediated immunity. These studies may reveal a possible role for HRA in the elicitation of cutaneous basophil hypersensitivity (CBH). The guinea pig will be used to further investigate the role of the basophil and its mediators in CBH and delayed hypersensitivity reactions. Different dose, adjuvant and temporal conditions will be used to evoke distinct states of sensitization. The contribution of antigen-induced histamine release, IgE and IgG antibody titers, and the production of chemotactic and histamine releasing activities by lymphocytes will be determined. Drugs will also be employed to further dissect the mechanisms of these reactions.